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Challenges of Regulation and Risk Assessment of Nanomaterials

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Biokinetics <strong>of</strong> Manufactured <strong>Nanomaterials</strong> in vivo<br />

Kreyling W.G. 1<br />

1Helmholtz Center Munich - Research Center for Environmental Health; Comprehensive Pneumology Center -<br />

Institute <strong>of</strong> Lung Biology <strong>and</strong> Disease <strong>and</strong> Focus Network NanoHealth, 85764 Neuherberg / Munich, Germany<br />

The inhalation <strong>and</strong> deposition <strong>of</strong> Nanoparticles (NP) in the respiratory tract provides a direct route <strong>of</strong><br />

intake into the organism by crossing the air-blood-barrier.<br />

To quantitatively determine accumulated NP fractions in such organs the ultimate aim is to balance<br />

the NP fractions in all interesting organs <strong>and</strong> tissues including the remaining body <strong>and</strong> total excretion.<br />

Since these gross determinations <strong>of</strong> NP contents in organs <strong>and</strong> tissues do not provide microscopic<br />

information on the anatomical <strong>and</strong> cellular location <strong>of</strong> nanoparticles such studies are to be<br />

complemented by electron microscopy analysis as demonstrated for inhaled titanium dioxide<br />

nanoparticles.<br />

After inhalation <strong>of</strong> various 20 nm NP aerosols (iridium, carbon, titanium dioxide, gold) <strong>and</strong> based on<br />

quantitative biokinetics in rats we found small NP fractions in all secondary organs studied including<br />

brain, heart. Fractions per secondary organ were usually below 0.1 % <strong>of</strong> the administered dose but<br />

depended strongly on particle NP parameters. Interestingly NP which had crossed the ABB showed<br />

different patterns <strong>of</strong> organ distribution compared to intravenously injected NP supporting the<br />

hypothesis that the formation <strong>and</strong> the dynamics <strong>of</strong> protein conjugation mediate the fate <strong>of</strong> NP in the<br />

organism.<br />

Current knowledge on systemic translocation <strong>of</strong> NP <strong>and</strong> their accumulation in secondary target<br />

organs <strong>and</strong> tissues <strong>of</strong> man <strong>and</strong> animal models does not suggest to cause acute effects <strong>of</strong> translocated<br />

NP but chronic exposure may lead to elevated NP accumulations resulting eventually in adverse<br />

health effects; these are likely to be triggered by mediators released in the lungs being the organ <strong>of</strong><br />

intake.<br />

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